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What remains unknown are the activating signals in glia, and how paracrine signals may be selective for a targeted neuron while sparing other proximate neurons. We studied these questions in the retina, where M\u00fcller glia contacts photoreceptors on one side and retinal ganglion cells on the other. In a mutant Rhodopsin mouse model of retinitis pigmentosa (RP) causing progressive photoreceptor death\u2014but sparing retinal ganglion cells\u2014TrkC.T1 and NT-3 ligand are upregulated in M\u00fcller glia. TrkC.T1 activity generates p-Erk, which causes increased TNF-\u03b1. These sequential events take place predominantly in M\u00fcller fibers contacting stressed photoreceptors, and culminate in selective death. Each event and photoreceptor death can be prevented by reduction of TrkC.T1 expression, by pharmacological antagonism of TrkC or by pharmacological inhibition Erk. Unmasking the sequence of non-cell autologous events and mechanisms causing selective neuronal death may help rationalize therapies.<\/jats:p>","DOI":"10.1038\/s41419-017-0074-8","type":"journal-article","created":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T15:23:49Z","timestamp":1513265029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["In retinitis pigmentosa TrkC.T1-dependent vectorial Erk activity upregulates glial TNF-\u03b1, causing selective neuronal death"],"prefix":"10.1038","volume":"8","author":[{"given":"Alba","family":"Gal\u00e1n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Jmaeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo F.","family":"Barcelona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fouad","family":"Brahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinko V.","family":"Sarunic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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